The present invention relates to viscoelastic systems and methods of use. In particular, the present invention relates to switchable viscoelastic systems comprising compositions containing galactomannan polymers and borates. In general, the switchable viscoelastic systems are administered as a Part I viscous liquid during surgery, followed by the addition of a Part II gel-activating composition to the in situ Part I composition. The activation of the system provides a gel, allowing for the easy and complete removal of the viscoelastic system by aspiration.
Viscoelastic systems or materials generally comprise a polymer or mixture of polymers which exhibit both a viscous (adhesive) character and an elastic (cohesive) character. These compositions are useful for surgery because they provide some level of coatability to the tissues to be protected, and also are somewhat cohesive, allowing for aspiration of the composition following the termination of surgery. Viscoelastic compositions are useful in a number of different surgeries and, in particular, ocular surgeries.
Cataracts are opacities of the ocular lens which generally arise in the elderly. In order to improve eyesight, the cataractous lens is removed and an intraocular lens (xe2x80x9cIOLxe2x80x9d) is inserted into the capsular bag. In order to maximize the procedure and post-surgical recovery, viscoelastic materials are injected in the anterior chamber and capsular bag to prevent collapse of the anterior chamber and to protect tissue from damage resulting from physical manipulation.
Trabeculectomy, i.e., glaucoma filtration surgery, involves the surgical creation of a fistula with a conjunctival flap which allows the direct drainage of aqueous humor from the anterior chamber into the conjunctival tissue. This procedure is used as an alternative to drug therapy, and allows for an increase in outflow of aqueous humor, thereby lowering the elevated intraocular pressure associated with glaucoma. In order to maintain a deep chamber and enhance visualization during the surgery, viscoelastic systems have been injected into the anterior chamber of the eye. The viscoelastic material used for such procedure may be difficult to aspirate out of the chamber following surgery. Ineffective or delayed removal of xe2x80x9clostxe2x80x9d viscoelastic material in the anterior chamber can clog the natural drainage pores of the trabecular meshwork and actually lead to increased intraocular pressure. Thus, a need exists for the provision of improved viscoelastic compositions which are easily aspirated following filtration bleb surgery.
Vitrectomy surgery can also induce a variety of post-surgical complications. Many of these complications are further potentiated in diabetic patients who are at risk for many ocular pathologies. Due to the severity of the surgical procedure, the posterior segment surgery process can cause extensive tissue damage at both the acute and chronic phases of the recovery. The chronic phase of the postsurgical period is characterized by more severe complications that can necessitate additional surgery. These include an incidence of recurrent retinal detachment, epiretinal proliferation, neovascular glaucoma, corneal problems, vitreous hemorrhage, cystoid macular edema, and occurrence of cataract formation within six months of surgery. While various surgical irrigating and viscoelastic compositions are employed, the frequency of above-described complications still needs to be lessened by facilitating the recovery of vascular leakage and limiting the duration of the cellular proliferative response. Therefore, a need exists to improve the current effectiveness of viscoelastic compositions used in vitrectomy surgery.
Various viscoelastic compositions are available for surgical use. These compositions have employed various viscoelastic agents, such as sodium hyaluronate, chondroitin sulfate, polyacrylamide, HPMC, proteoglycans, collagen, methylcellulose, carboxymethyl cellulose, ethylcellulose, polyvinylpyrrolidone and keratan, all of various molecular weights and concentrations, and/or combinations thereof.
Those skilled in the art have formulated compositions containing the various viscoelastic agents described above to suit their particular needs. The suitability of a given agent has depended on the various function(s) which the agent is expected to perform and the surgical technique being employed by the surgeon. For example, for portions of surgical procedures involving phacoemulsification and tissue manipulation, e.g., cataract surgery, it has been generally preferable to use a viscoelastic agent that possesses relatively greater tissue coatability (xe2x80x9cadherentxe2x80x9d or xe2x80x9cadhesivexe2x80x9d) properties and, consequently, relatively lesser cohesive properties. Those portions of surgical procedures involving manipulation of an IOL are generally better served by viscoelastic agents that possess relatively greater cohesive properties and relatively lesser adherent properties to maintain space. Such agents are referred to herein as xe2x80x9ccohesivexe2x80x9d agents.
Various viscoelastic agents have been employed in an effort to provide the above-described needs. For example, 5% HPMC provides good coatability for tissue protection. However, since tissue adhesion of this polymer is high, HPMC is more difficult to remove from the tissue, and such efforts of removal may adversely affect the tissue. This is also particularly critical in ocular surgery, as a residue of viscoelastic agent remaining in the eye following surgery can block the natural flow of aqueous humor and possibly induce glaucoma. On the other hand, polymers with a high degree of elasticity (cohesiveness) have provided ease and complete removal of the viscoelastic agent. However, these highly cohesive agents do not provide the proper level of coatability and hence, only provide a limited level of tissue protection. Thus, in most cases, it is desired to employ agents which possess extremes of both properties.
Since adhesion and cohesion properties are inversely related (i.e., increasing one property decreases the other), current viscoelastic agents do not possess a high degree of both properties, but in general, tend to exhibit a far greater magnitude of one property and considerably less character of the other property, or compromise between the two properties. In order to exploit the advantages of both types of properties, practitioners have employed viscoelastic regimens which employ two different compositions containing the different types of agents (see, e.g., U.S. Pat. No. 5,273,056 (McLaughlin et al.)).
The present invention is directed to switchable viscoelastic systems. The viscoelastic systems of the present invention comprise a two-part gelable system, wherein the gel is created by the variable crosslinking of a borate compound with one or more galactomannans. The gelation is completely reversible by manipulating pH.
In use, a Part I composition, containing one or more galactomannans in the presence or absence of a borate compound, is administered during surgery as an adherent composition. When the next phase of surgery is to be initiated, the Part II composition, comprising a crosslinking amount of a borate compound, is administered to the in situ Part I composition, thereby activating or further activating the gelation of the galactomannan containing composition. The admixture of Part I and II forms a highly cohesive composition which provides space maintenance capabilities and easy aspiration of the viscoelastic system at the close of surgery.
The viscoelastic systems of the present invention provide the advantages of a switchable gelling system, wherein a composition may be administered as a liquid or partially gelled liquid and later converted to a gel. Accordingly, one advantage of the viscoelastic systems of the present invention is that they provide optimal levels of both adhesive properties and cohesive properties in a single system. Another advantage of the systems is that they are switchable, i.e., they may be converted from an adherent system to a cohesive system during surgery. Current viscoelastic compositions have employed hyaluronic acid and other naturally occuring polymers. The preparation and sterilization of these agents is generally expensive, resulting in relatively expensive viscoelastic compositions. The systems of the present invention comprise relatively inexpensive agents. Thus, another advantage of the systems of the present invention is that they are relatively low in cost to produce. Still another advantage of the systems of the present invention is that they provide a relatively high degree of reproducibility of the gel charcteristics through various types and sources of galactomannan (see, FIG. 3). This feature allows for the interchange of sourcing without extensive reworking of the compositions of the present invention.
The methods of the present invention involve the surgical use of the compositions of the present invention.
The present invention is also directed to methods of sterilization of the galactomannans involving autoclaving.